Dental caries (also known as tooth decay) remains the most common chronic disease of childhood. Although overall caries prevalence has declined over the last 40 years, dental caries in the primary dentition and mean caries rates in children ages 2-11 has increased markedly over the past 12 years. Childhood caries is a serious public health issue because of associated health problems and because disparities in oral health have led to substantially higher average disease prevalence among children in poverty and in underserved racial and ethnic groups. These issues are of such concern that in 2005, the American Academy of Pediatrics made children's oral health one of their top areas of focus, as it is for the majority of the NIDCR "Disparities Centers." Multiple factors contribute to a person's risk for caries, including environmental factors such as diet, oral hygiene, fluoride exposure and the level of colonization of cariogenic bacteria and host factors such as salivary flow. There are still individuals who appear to be more susceptible to caries and those that are extremely resistant, regardless of the environmental risk factors to which they are exposed, implying that genetic factors also play an important role in caries etiology. This conclusion is supported by studies in both humans and animals, with the most compelling evidence coming from studies of twins reared apart in which investigators found significant resemblance within monozygotic (MZ) but not dizygotic (DZ) twin pairs for percentage of teeth and surfaces restored or carious and estimated the genetic contribution to caries as 40%. Despite the strong evidence of a genetic component to risk for dental caries, there have been only a few studies of candidate genes in caries, and no published genome-wide scans. Therefore, the goal of this study is to perform genome-wide association (GWA) studies of dental caries with a large panel of SNPs (500,000 or more) in families and individuals ascertained through multiple US sites. There will be an initial GWA scan in samples from three sites (University of Pittsburgh, University of Iowa, and University of Washington), with follow-up studies in additional collaborating sites (University of Michigan and UCSF). Successful completion of this study will allow a better understanding of the biology of dental caries, and will lead to earlier identification of children at risk for dental caries, thereby allowing improved and targeted interventions.